Perioperative fuzuloparib plus mFOLFIRINOX for resectable pancreatic adenocarcinoma: A phase 1 study.

4163 Background: Surgical resection followed by adjuvant mFOLFIRINOX is currently the standard of care for resectable pancreatic adenocarcinoma. Neoadjuvant therapy has the potential to induce tumor downsizing and improve R0 resection rate. In this study, we aimed to explore the feasibility of the PARP inhibitor fuzuloparib in combination with mFOLFIRINOX as the neoadjuvant and adjuvant therapy in patients (pts) with resectable pancreatic adenocarcinoma. Methods: This was a dose escalation and expansion phase 1 study in pts with histologically or cytologically confirmed, high-risk resectable or borderline resectable pancreatic adenocarcinoma. Eligible pts received perioperative treatment with fuzuloparib plus mFOLFIRINOX (up to 12 cycles of 14 days each, with 4 to 6 cycles administered preoperatively; fuzuloparib at escalating doses starting at 30 mg BID), followed by maintenance fuzuloparib at 150 mg BID. Dose-limiting toxicities (DLTs) were observed during the first 2 treatment cycles. The primary objectives were safety and tolerability. Results: As of Oct 31, 2023, 15 pts were enrolled, including 3 pts in the fuzuloparib 30 mg cohort and 12 pts in the 60 mg cohort. Twelve (80.0%) pts completed neoadjuvant therapy as planned. Eight (53.3%) pts underwent surgical resection, and all pts achieved R0 resections (100.0%; 95% CI, 63.1–100.0). Four of the 8 (50.0%) pts proceeded to adjuvant therapy (30 mg cohort: 0/2 0%; 60 mg cohort: 4/6 66.7%). There were no DLTs identified. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 12 (80.0%) pts, with the most common being decreased neutrophil count, decreased white blood cell count, hypokalemia, and anemia. No unexpected TRAEs were reported. No patients discontinued study treatment due to TRAEs. Conclusions: Perioperative fuzuloparib plus mFOLFIRINOX was generally tolerated and had acceptable safety profile in pts withresectable pancreatic adenocarcinoma. Neoadjuvant fuzuloparib plus mFOLFIRINOX prior to surgery achieved a R0 resection rate of 100%. Clinical trial information: NCT04425876 .